Allergy Testing Test Request and Result Interpretation Dr. Kareena Schnabl, MSc, PhD, FCACB Clinical Biochemist, Genetic Laboratory Services University of Alberta Hospital Newborn Screening & Biochemical Genetics Laboratory Department of Laboratory Medicine & Pathology Laboratory Medicine Symposium, June 15, 2013 Learning Objectives By the end of this presentation you will: Know which test to request for allergy testing and the process Be confident with your interpretation of allergy test results 1
Allergy Testing Challenges in Alberta Increased prevalence of atopic disorders and shortage of allergy specialists Difficult to diagnose and treat Primary care, self diagnosis and treatment Processes, procedures, and policies for allergy testing outdated and not in-line with new/updated guidelines Inappropriate test use and variation in clinical practice Suboptimal performance of some allergy tests Significant impact on patients Financial burden to the healthcare system Send Out Test Audit for Allergen Specific IgE Number of tests % Number of Tests % Negative Results Total 319 100% 72% Allergist Clinical Immunologist 94 29% 46% Other 225 71% 83% 2
Classification of Adverse Reactions to Food ADVERSE FOOD REACTION Toxic Non-Toxic Food Allergy (Immune) Food Intolerance (Non-Immune) IgE Mixed Non IgE-mediated Pharmacological Metabolic Food allergy, allergic rhinitis Oral allergy syndrome Anaphylaxis Eosinophilic esophagitis Atopic dermatitis Celiac disease Psychological Idiosyncratic World Allergy Organization, Allergology International 2009; 58:457 66. Curr Gastroenterol Rep (2011) 13:426 434 Most Common Food Allergies 8 foods are responsible for 90% of all food allergies Infants and Young Children (6 8%) Teens and Adults (2 4%) Cow s Milk Egg White Shellfish Mollusca Crustacea Peanut (legume) Tree Nuts Wheat Soy (legume) Peanut Tree Nuts Fish Food Reactions: Food Allergy 10% Food Intolerance 15% 3
Natural History of Allergies Atopic March (World Allergy Organization) Co existing IgE diseases: food allergy, atopic dermatitis, eosinophilic esophagitis, allergic rhinitis, asthma Children often outgrow food allergies (develop tolerance) to milk, egg, soy and wheat. Food allergies to peanuts, tree nuts, shellfish and fish often persist. Immunotherapy may alter the natural history of allergic rhinitis Avoidance of triggers and medications help manage persistent food allergies and asthma Pediatr Adolesc Health Care 2009;39:236 54, J Aller Clin Immun 2004;113:805 19. Diagnosis of IgE Mediated Allergy Medical history and physical examination Identify causative allergen Multiple symptoms occur within minutes to hours, anaphylaxis Co existing atopic disorder Guides diagnostic test selection Test identifies causative allergen (sensitization, IgE mediated) skin prick test (SPT), rarely intradermal test serum allergen specific IgE antibody (sige) SPT or sige alone are not diagnostic Confirmatory diagnostic tests spirometry (asthma) oral food challenge (food allergy) Serum total IgE Food screen Food specific IgG elimination diet, skin or GI biopsy, histology (mixed or non IgE) National Institute of Allergy and Infectious Disease Guidelines for Food Allergy Diagnosis 2010, CSACI Position Statement on Food-Specific IgG 4
Serum Allergen Specific IgE (sige) 1972 RadioAllergoSorbent Test (RAST) - term used incorrectly, abandon 1980 s Automated fluoroenzyme immunoassays Indirect measurement of circulating IgE antibodies to specific allergens, more specific than total IgE Edmonton (DL) and Calgary (CLS) use the same platform and numeric cut-off Pediatrics 2012; 129:193-97, J Allergy Clin Immunol 2010;126(1):33-38. Test Menu, Performance and Cost Multi-allergen sige screens (qualitative, $17.16 per screen) Inhalant screen Allergic symptoms but causative allergen unknown, order once Good rule-out test (93% sensitivity, 89% specificity) Positive screen reflexes to inhalant panel Food screen (>20,000 per year) and reflex food panel discontinuation Poor sensitivity and specificity (high false positive rate) Broad screening for foods is not supported by guidelines Individual allergen sige (quantitative, $17.16 per allergen) Inhalant, antibiotic and insect venom panels Specific food, inhalant, and latex allergens More sensitive and specific than multi-allergen screens 5
Clinical Utility of Serum Allergen Specific IgE Indicates sensitization to a particular allergen not clinical allergy Good performance for most foods, pollen, dust mite and latex Complimentary to skin tests for animal dander, molds, insect venoms and drugs Levels correlate with an increased likelihood of clinical allergy not allergic severity Monitor for development of tolerance High initial sige associated with lower rate of resolution of clinical allergy Monitor every 6 months to a year Pediatrics 2012; 129:193-97, J Allergy Clin Immunol 2010; 126:33-8, Ann Allergy Asthma Immunol 2008; 101:580-92. 6
Reporting/Interpretation of sige Results Negative (<0.35kU/L) A negative allergen specific IgE antibody test should not be used alone to reject a diagnosis of allergy. It is possible for a patient to have significant allergy yet have a negative test. Results must be interpreted within the clinical context of the patient. Positive Detection of IgE antibodies in the serum (sensitization) indicates a greater likelihood of clinical allergy and identifies the allergens that may be responsible for symptoms. Clinical correlation is required. Consider referral to an allergist. Insufficient information provided on the requisition. Test cancelled. Guidelines recommend selection of individual allergens based on patient history. Serum Allergen Specific IgE Testing Strengths Limitations Available in primary care office One sample, many results Less invasive Quantitative, reproducible Antihistamines are ok No risk of reaction Often non-allergists order test Test selection requires patient history Broad screening - expensive Delayed results Challenge interpreting results (sensitization vs. clinical allergy) Patients with skin condition Sensitivity/specificity varies by Young child or geriatric allergen patient Cross reactivity Pediatrics 2012; 129:193 97, J Allergy Clin Immunol 2010; 126:33 8, Ann Allergy Asthma Immunol 2008; 101:580 92. 7
Future Directions Family physician and pediatrician feedback on requisition Audit for test utilization and performance Provincial allergy testing working group Educational materials Guidelines Policy Component resolved diagnostics Allergen extract quality Cross reactivity Allergic severity Acknowledgements DynaLIFE Dx Allergy testing working group Allergists/Clinical Immunologists/Respirologists Dr. Stuart Carr, Dr. Tim Vander Leek, Dr. Per Lidman, Dr. Harissios Vliagoftis, Dr. Joel Doctor, Dr. Dilini Vethanayagam Medical laboratory science students Ms. Agnes Tan and Ms. Raluca Maries Alberta Health Services and Calgary Laboratory Services Somagen, General Practitioners, Dieticians and Families 8
Clinical Utility of Serum Total IgE Non specific and not recommended by guidelines for use as a screen or diagnostic test for atopic disorders Screen and diagnosis of Allergic Bronchopulmonary Aspergillosis Omalizumab dose for treatment of persistent severe asthma Baseline serum total IgE (30 700kU/L) and patient s body weight Parasite infections Cancer Immunodeficiency sige Levels & Probability of Clinical Allergy 9
Allergen Cross Reactivity other shellfish 75% 10